Unusual Presentation of Simple Virilising Congenital Adrenal - PDF document

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/303898335 Unusual Presentation of Simple Virilising Congenital Adrenal Hyperplasia as a Testicular Adrenal Rest Tumor Article in Ibnosina Journal of Medicine and Biomedical Sciences · January 2014 DOI: 10.4103/1947-489X.210396 CITATIONS READS 0 86 6 authors , including: Asma Deeb Emad Moussa Mafraq Hospital - Abu Dhabi Al Noor Hospital 105 PUBLICATIONS 1,043 CITATIONS 1 PUBLICATION 0 CITATIONS SEE PROFILE SEE PROFILE Ieuan A Hughes University of Cambridge 325 PUBLICATIONS 14,535 CITATIONS SEE PROFILE Some of the authors of this publication are also working on these related projects: Registries for rare endocrine conditions View project Childhood obesity comorbidities View project All content following this page was uploaded by Asma Deeb on 11 June 2016. The user has requested enhancement of the downloaded file.

Deeb A et al Congenital Adrenal Hyperplasia in the testicle 313 CASE REPORT Unusual Presentation of Simple Virilising Congenital Adrenal Hyperplasia as a Testicular Adrenal Rest Tumor Asma Deeb 1 , Azaz Khan 2 , Amin Gawhary 3 , Muhannad Al-Zubaidi 4 , Emad Moussa 5 , Ieuan A Hughes 6 1 Paediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, UAE 2 Paediatric Department, Al Ruwais Hospital, Abu Dhabi, UAE 3 Paediatric Surgery Department, Al Noor Hospital, Abu Dhabi, UAE 4 Histopathology Department, Al Noor Hospital, Abu Dhabi, UAE 5 Radiology Department, Al Noor Hospital, Abu Dhabi, UAE 6 Department of Pediatrics, University of Cambridge, Cambridge, UK Corresponding author: Dr Asma Deeb Email: adeeb@mafraqhospital.ae Published: 22 November 2014 Ibnosina J Med BS 2014;6(6):313-317 Received: 06 June 2014 Accepted: 18 July 2014 This article is available from: http://www.ijmbs.org This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 License, which per- mits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Testicular adrenal rest tumors are commonly seen in Testicular adrenal rest tumors (TART) in patients with congenital adrenal hyperplasia. The tumors are typically CAH were fjrst described by Wilkins in 1940 (1). Now with bilateral and arise from ACTH dependent aberrant adrenal the use of ultrasound, their prevalence in CAH is common cells in the testes. Diagnosis is clinically confjrmed by (2). It is hypothesized that TART arises from aberrant ultrasound imaging. These tumors are characterized by their adrenal cells that descend with the testes during embryonic response to steroid replacement and biopsy is not routinely development and can be seen in normal male infants (3). required. Differentiating the tumor from Leydig cell tumor The tumors form under infmuence of raised ACTH levels can be diffjcult. Management and prognosis for these two acting on aberrant cells. Ultrasound scan is the method of pathologies are different, so extensive investigations may choice for detection of TART because it is readily available be required to confjrm the diagnosis. We present a 5 year old and enables small tumors to be detected (4). In one study, boy who had an unusual presentation of a testicular tumor TARTs were detected in 16 out of 17 patients with CAH and detail the investigations undertaken to differentiate a in whom only 6 were palpable (5). An adrenal rest tumor testicular adrenal rest tumor from a Leydig cell tumor. can clinically mimic a Leydig cell tumor, leading to unnecessary orchidectomy. A correct diagnosis is essential Key words: Congenital adrenal hyperplasia (CAH), as a Leydig cell tumor is potentially malignant. Although testicular adrenal rest tumor (TART), Leydig cell tumor, TART may resemble a Leydig cell tumor histologically, Synoptophysin the former contains sheets, nests, and cords of cells with abundant eosinophilic cytoplasm. These cells may contain Ibnosina Journal of Medicine and Biomedical Sciences (2014)

Ibnosina J Med BS 314 lipochrome pigment, but Reinke crystalloids, characteristic of Leydig cells, are absent. TART also shows features of low mitiotic activity, extensive fjbrosis, lymphoid aggregates, adipose metaplasia and prominent lipochrome. In addition to histology, immunohistochemistry may be a distinguishing feature (6). Case report Presentation We report a 5 year old boy who was referred with a suspected testicular tumor. At 4.5 years, examination revealed genital staging of G4 and a pubic hair of PH 3 (Fig. 1). Testicular size was 4 and 2 ml for the right and the left sides, respectively. Both testes were of normal Figure 2. Sagittal sonogram of the right testis demonstrating multiple hypo echoic intra testicular infjltrates at the upper pole extending from the hilar region toward the center of the testis. Figure 1. Appearance of genitalia with features of precocious puberty consistency and there was no discrete mass palpable in the right testis. Growth velocity was accelerated at 10cm/yr. He was normotensive and the rest of the examination was Figure 3. Axial T2 MRI scan demonstrating small hypo intense normal. foci near the testicular hilar zone with hypo intense infjltrates at the upper pole of the right testis at the posterior zone. Investigations Initial investigations showed an early pubertal level pole of the right testis measuring 1.2 x 0.98 cm (Fig 2). of testosterone (1.5 nmol/L), but prepubertal levels of There was no calcifjcation or appreciable vascularity on gonadotrophins. In contrast, serum 17OH-progesterone complementary Doppler workup. MRI showed multiple (17OHP) was markedly elevated at 426 nmol/l (NR 0.6-6.8 hypoechoic intratesticular infjltrates at the upper pole nmol/ml). Tumor markers; hCG and alpha fetoprotein were extending from the hilar region towards the center of the negative. Bone age was 11 years at a chronological age of testis, the largest measuring 12x9 mm diameter (Fig 3). 5 years. Ultrasound of the testes revealed a hypoechoic In view of the elevated 17OHP level, a sequencing screen diffuse, irregular inhomogenous lesion at the upper of the CYP21A2 gene was performed. It tests for gene ISSN: 1947-489X www.ijmbs.org

Deeb A et al Congenital Adrenal Hyperplasia in the testicle 315 Figure 4. Macroscopic appearance of TART prior to biopsy Figure 6. Immunohistochemistry showing strong uptake of Synoptophysis stain. 17OHP had decreased to 46 nmol and a repeat ultrasound showed a reduction in the size of the testicular mass to 0.6 X 0.6 cm. Since TART is usually bilateral, a biopsy of the right testis was performed to exclude a Leydig cell tumor. Macroscopically, a mass measuring 1.2 x 0.7 cm in aggregate with brownish nodular homogenous cut surface was seen at the upper pole of the right testis (Fig. 4). On histology, the tumor cells had well-defjned outlines with deeply acidophilic but occasionally clear cytoplasm, and a round or oval nuclei . The cells were arranged in sheets, nests, and cords with abundant eosinophilic cytoplasm and contained lipochrome pigment. Reinke crystalloids were absent. The mass lacked fjbrous bands, atypia, necrosis and mitosis. The seminiferous tubules were surrounded by the lesion (Fig. 5). Immunohistochemistry staining using Synoptophysin showed strong diffuse reactivity (Fig. 6). Figure 5. Hematoxylin and Eosin stain showing seminiferous tubules surrounded by cells arranged in sheets, nests and cords Outcome and follow-up with abundant eosinophilic cytoplasm. Puberty had progressed further with an LHRH stimulation test demonstrating gonadotrophin -dependent precocious copy number, gene to pseudogene conversion, 7 common puberty. Consequently, treatment with a gonadotrophin point mutations and the exon 6 cluster of mutations. This analogue was started at the age of 7 years. sequencing screen detects about 90% of mutations causing 21-hydroxylase defjciency. In this particular case, no Discussion mutation was identifjed. Diagnosis in this child presented a clinical dilemma because of some unusual features. The diagnosis of CAH Treatment and further investigations was only made after presenting with a testicular mass The clinical diagnosis was consistent with simple virilising consistent with TART. Generally, a diagnosis of CAH CAH associated with a unilateral TART. Treatment with is already known prior to the detection of the testicular hydrocortisone, 12 mg/m 2 /day in three divided doses, was tumors. However, there are reports where detection of the started to suppress the 17OHP level. Six months later, serum tumor has led to the diagnosis of CAH (7). CAH in this Ibnosina Journal of Medicine and Biomedical Sciences (2014)